scholarly journals ETBreceptor contribution to vascular dysfunction in postmenopausal women

2017 ◽  
Vol 313 (1) ◽  
pp. R51-R57 ◽  
Author(s):  
Megan M. Wenner ◽  
Kelly N. Sebzda ◽  
Andrew V. Kuczmarski ◽  
Ryan T. Pohlig ◽  
David G. Edwards
Keyword(s):  
Receptor Antagonist ◽  
Postmenopausal Women ◽  
Vascular Dysfunction ◽  
Local Heating ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Age Related ◽  
Measured Flow ◽  
Vasodilatory Function ◽  
Cutaneous Vascular Conductance

Endothelin-1 (ET-1) contributes to age-related endothelial dysfunction in men via the ETAreceptor. However, there are sex differences in the ET-1 system, and ETBreceptors are modulated by sex hormones. The purpose of this study was to test the hypothesis that ETBreceptors contribute to impaired vasodilatory function in postmenopausal women (PMW). We measured flow-mediated dilation (FMD) using ultrasound, and cutaneous nitric oxide-mediated vasodilation during local heating (42°C) via laser Doppler flowmetry in 18 young women (YW; 22 ± 1 yr) and 16 PMW (56 ± 1 yr). Cutaneous microdialysis perfusions of lactated Ringer (control), an ETBreceptor antagonist (BQ-788, 300 nM), and an ETAreceptor antagonist (BQ-123, 500 nM), were done through separate fibers, followed by perfusions of sodium nitroprusside (28 mM) and local heating to 43°C (max). Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/mean arterial pressure and expressed as a percent of maximal dilation. FMD (YW: 7.5 ± 0.5 vs. PMW: 5.6 ± 0.6%) and cutaneous vasodilation (YW: 93 ± 2 vs. PMW: 83 ± 4%CVCmax) were lower in PMW (both P < 0.05). Blockade of ETBreceptors decreased cutaneous vasodilation in YW (87 ± 2%CVCmax; P < 0.05 vs. control) but increased vasodilation in PMW (93 ± 1%CVCmax; P < 0.05 vs. control). ETAreceptor blockade had minimal effect in YW (92 ± 1%CVCmax) but increased cutaneous vasodilation in PMW (91 ± 2%CVCmax; P < 0.05 vs. control). In conclusion, ETBreceptors mediate vasodilation in YW, but this effect is lost after menopause. Impaired vasodilatory function in PMW is due in part to a loss of ETB-mediated dilation.

scholarly journals Blunted increases in skin sympathetic nerve activity are related to attenuated reflex vasodilation in aged human skin

2016 ◽  
Vol 121 (6) ◽  
pp. 1354-1362 ◽  
Author(s):  
Anna E. Stanhewicz ◽  
Jody L. Greaney ◽  
Lacy M. Alexander ◽  
W. Larry Kenney
Keyword(s):  
Older Adults ◽  
Sympathetic Nerve Activity ◽  
Local Heating ◽  
Doppler Flowmetry ◽  
Healthy Older Adults ◽  
Cutaneous Vasodilation ◽  
Age Related ◽  
Dorsum Of Foot ◽  
Reflex Cutaneous Vasodilation ◽  
Cutaneous Vascular Conductance

Reflex cutaneous vasodilation in response to passive heating is attenuated in human aging. This diminished response is mediated, in part, by age-associated reductions in endothelial function; however, the contribution of altered skin sympathetic nervous system activity (SSNA) is unknown. We hypothesized that 1) healthy older adults would demonstrate blunted SSNA responses to increased core temperature compared with young adults and 2) the decreased SSNA response would be associated with attenuated cutaneous vasodilation. Reflex vasodilation was elicited in 13 young [23 ± 1 (SE) yr] and 13 older (67 ± 2 yr) adults using a water-perfused suit to elevate esophageal temperature by 1.0°C. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome (the dorsum of foot) were continuously measured. SSNA was normalized to, and expressed as, a percentage of baseline. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure and expressed as a percentage of maximal CVC (local heating, 43°C). Reflex vasodilation was attenuated in older adults ( P < 0.001). During heating, SSNA increased in both groups ( P < 0.05); however, the response was significantly blunted in older adults ( P = 0.01). The increase in SSNA during heating was linearly related to cutaneous vasodilation in both young ( R2 = 0.87 ± 0.02, P < 0.01) and older ( R2 = 0.76 ± 0.05, P < 0.01) adults; however, slope of the linear regression between ΔSSNA and ΔCVC was reduced in older compared with young (older: 0.05 ± 0.01 vs. young: 0.08 ± 0.01; P < 0.05). These data demonstrate that age-related impairments in reflex cutaneous vasodilation are mediated, in part, by blunted efferent SSNA during hyperthermia.

Local ascorbate administration augments NO- and non-NO-dependent reflex cutaneous vasodilation in hypertensive humans

2007 ◽  
Vol 293 (2) ◽  
pp. H1090-H1096 ◽  
Author(s):  
Lacy A. Holowatz ◽  
W. Larry Kenney
Keyword(s):  
Local Heating ◽  
Oxidant Stress ◽  
Control Site ◽  
No Synthase ◽  
Oral Temperature ◽  
Antioxidant Supplementation ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Reflex Cutaneous Vasodilation ◽  
Cutaneous Vascular Conductance

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated with essential hypertension. Decreased NO-dependent VD may be due to 1) increased oxidant stress and/or 2) decreased l-arginine availability through upregulated arginase activity, potentially leading to increased superoxide production through uncoupled NO synthase (NOS). The purpose of this study was to determine the effect of antioxidant supplementation (alone and combined with arginase inhibition) on attenuated NO-dependent reflex cutaneous VD in hypertensive subjects. Nine unmedicated hypertensive [HT; mean arterial pressure (MAP) = 112 ± 1 mmHg] and nine age-matched normotensive (NT; MAP = 81 ± 10 mmHg) men and women were instrumented with four intradermal microdialysis (MD) fibers: control (Ringer), NOS inhibited (NOS-I; 10 mM NG-nitro-l-arginine), l-ascorbate supplemented (Asc; 10 mM l-ascorbate), and Asc + arginase inhibited [Asc+A-I; 10 mM l-ascorbate + 5 mM ( S)-(2-boronoethyl)-l-cysteine-HCl + 5 mM Nω-hydroxy- nor-l-arginine]. Oral temperature was increased by 0.8°C via a water-perfused suit. NG-nitro-l-arginine was then ultimately perfused through all MD sites to quantify the change in VD due to NO. Red blood cell flux was measured by laser-Doppler flowmetry over each skin MD site, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/MAP) and normalized to maximal CVC (%CVCmax; 28 mM sodium nitroprusside + local heating to 43°C). During the plateau in skin blood flow (ΔTor = 0.8°C), cutaneous VD was attenuated in HT skin (NT: 42 ± 4, HT: 35 ± 3 %CVCmax; P < 0.05). Asc and Asc+A-I augmented cutaneous VD in HT (Asc: 57 ± 5, Asc+A-I: 53 ± 6 %CVCmax; P < 0.05 vs. control) but not in NT. %CVCmax after NOS-I in the Asc- and Asc+A-I-treated sites was increased in HT (Asc: 41 ± 4, Asc+A-I: 40 ± 4, control: 29 ± 4; P < 0.05). Compared with the control site, the change in %CVCmax within each site after NOS-I was greater in HT (Asc: −19 ± 4, Asc+A-I: −17 ± 4, control: −9 ± 2; P < 0.05) than in NT. Antioxidant supplementation alone or combined with arginase inhibition augments attenuated reflex cutaneous VD in hypertensive skin through NO- and non-NO-dependent mechanisms.

Decreased nitric oxide- and axon reflex-mediated cutaneous vasodilation with age during local heating

2002 ◽  
Vol 93 (5) ◽  
pp. 1644-1649 ◽  
Author(s):  
Christopher T. Minson ◽  
Lacy A. Holowatz ◽  
Brett J. Wong ◽  
W. Larry Kenney ◽  
Brad W. Wilkins
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
The Elderly ◽  
Axon Reflex ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Age Related ◽  
Older Subjects ◽  
Initial Peak ◽  
Age Related Changes

Cutaneous vasodilation is reduced in healthy older vs. young subjects; however, the mechanisms that underlie these age-related changes are unclear. Our goal in the present study was to determine the role of nitric oxide (NO) and the axon reflexes in the skin blood flow (SkBF) response to local heating with advanced age. We placed two microdialysis fibers in the forearm skin of 10 young (Y; 22 ± 2 yr) and 10 older (O; 77 ± 5 yr) men and women. SkBF over each site was measured by laser-Doppler flowmetry (LDF; Moor DRT4). Both sites were heated to 42°C for ∼60 min while 10 mM N G-nitro-l-arginine methyl ester (l-NAME) was infused throughout the protocol to inhibit NO synthase (NOS) in one site and 10 mM l-NAME was infused after 40 min of local heating in the second site. Data were expressed as a percentage of maximal vasodilation (%CVCmax; 28 mM nitroprusside infusion). Local heating beforel-NAME infusion resulted in a significantly reduced initial peak (Y: 61 ± 2%CVCmax vs. O: 46 ± 4%CVCmax) and plateau (Y: 93 ± 2%CVCmaxvs. O: 82 ± 5%CVCmax) CVC values in older subjects ( P < 0.05). When NOS was inhibited after 40 min of heating, CVC declined to the same value in the young and older groups. Thus the overall contribution of NO to the plateau phase of the SkBF response to local heating was less in the older subjects. The initial peak response was significantly lower in the older subjects in both microdialysis sites (Y: 52 ± 4%CVCmax vs. O: 38 ± 5%CVCmax; P < 0.05). These data suggest that age-related changes in both axon reflex-mediated and NO-mediated vasodilation contribute to attenuated cutaneous vasodilator responses in the elderly.

Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin

2006 ◽  
Vol 291 (6) ◽  
pp. H2965-H2970 ◽  
Author(s):  
Lacy A. Holowatz ◽  
Caitlin S. Thompson ◽  
W. Larry Kenney
Keyword(s):  
Human Subjects ◽  
Whole Body ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Age Related ◽  
Aged Skin ◽  
Young Subjects ◽  
O 15 ◽  
Reflex Cutaneous Vasodilation ◽  
Cutaneous Vascular Conductance

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated in older humans. NO may be decreased by an age-related increase in reactive oxygen species or a decrease in l-arginine availability via upregulated arginase. The purpose of this study was to determine the effect of acute antioxidant supplementation alone and combined with arginase inhibition on reflex VD in aged skin. Eleven young (Y; 22 ± 1 yr) and 10 older (O; 68 ± 1 yr) human subjects were instrumented with four intradermal microdialysis (MD) fibers. MD sites were control (Co), NO synthase inhibited (NOS-I), l-ascorbate supplemented (Asc), and Asc + arginase-inhibited (Asc + A-I). After baseline measurements, subjects underwent whole body heating to increase oral temperature (Tor) by 0.8°C. Red blood cell flux was measured by using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure) and normalized to maximal (CVCmax). VD during heating was attenuated in O (Y: 37 ± 3 vs. O: 28 ± 3% CVCmax; P < 0.05). NOS-I decreased VD in both groups compared with Co (Y: 20 ± 4; O: 15 ± 2% CVCmax; P < 0.05 vs. Co within group). Asc and Asc + A-I increased VD beyond Co in O (Asc: 35 ± 4% CVCmax; Asc + A-I: 41 ± 3% CVCmax; P < 0.001) but not in Y (Asc: 36 ± 3% CVCmax; Asc + A-I: 40 ± 5% CVCmax; P > 0.05). Combined Asc + A-I resulted in a greater increase in VD than Asc alone in O ( P = 0.001). Acute Asc supplementation increased reflex VD in aged skin. Asc combined with arginase inhibition resulted in a further increase in VD above Asc alone, effectively restoring CVC to the level of young subjects.

scholarly journals Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation in humans by decreasing ascorbate-sensitive oxidants

2011 ◽  
Vol 301 (3) ◽  
pp. R763-R768 ◽  
Author(s):  
Lacy A. Holowatz ◽  
W. Larry Kenney
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
Oxidant Stress ◽  
Microvascular Dysfunction ◽  
Local Skin ◽  
Cutaneous Vasodilation ◽  
Before And After ◽  
Atorvastatin Therapy ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance

Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ≪ngname≫ was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVCmax, P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVCmax, P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVCmax, P < 0.001) or combined with arginase inhibition (96 ± 3% CVCmax, P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVCmax, both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVCmax, P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVCmax, P > 0.05) or combined with arginase inhibition (67 ± 4% CVCmax, P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.

Abstract P156: Estrogen Regulation of Endothelin-B Receptor Mediated Vasodilation

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Katherine Haigh ◽  
Ronald F Feinberg ◽  
Hugh S Taylor ◽  
Megan M Wenner
Keyword(s):  
Postmenopausal Women ◽  
Young Women ◽  
Local Heating ◽  
Receptor Blockade ◽  
Ovarian Hormone ◽  
Hormone Production ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
Etb Receptor ◽  
Endothelin B

Our laboratory has recently demonstrated that a loss of endothelin-B (ETB) receptor mediated dilation contributes to impaired vasodilatory function in postmenopausal women. It is unclear if these changes are due to aging, or alterations in ovarian hormones that occur after menopause. The purpose of this study was to test the hypothesis that in a low estradiol state, there is a loss of ETB mediated dilation, and that estradiol administration reverses these responses and mediates dilation. Methods: We tested 8 young women (YW: 24±2 years, 23±1 kg/m 2 , mean arterial BP 84±2mHg) and 6 postmenopausal women (PMW: 56±1 years, 24±1 kg/m 2 , mean arterial BP 94±2mHg). In YW, we suppressed endogenous ovarian hormone production with daily gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) administration for 10 days, adding estradiol (E2, 0.1 mg/day, Vivelle dot patch) on days 4-10. PMW were tested at baseline and after 1-week E2 administration (0.1 mg/day, Vivelle dot patch). We measured nitric-oxide mediated vasodilation in the cutaneous circulation during local heating (42°C) via laser Doppler flowmetry, followed by microdialysis perfusions of sodium nitroprusside (28mM) with local heating to 43°C to elicit maximal dilation. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/mean arterial blood pressure, and expressed as a percent of maximal dilation. Results: ETB receptor blockade increased vasodilation in YW during hormone suppression with GnRHant (control: 88±3 vs. BQ-788: 94±2 CVC %max, P <0.05). However, ETB receptor blockaded tended to reduce vaodilation during E2 administration (control: 88±3 vs. BQ-788: 82±2 CVC %max, P =0.12). In PMW, ETB receptor blockade had no significant effect on vasodilatory responses (control: 90±4 vs. BQ-788: 95±2 CVC %max, P =0.20). Similarly, ETB receptor blockade did not alter vasodilation after E2 administration (control: 88±7 vs. BQ-788: 88±4 CVC %max). Conclusions: These preliminary data suggest that suppression of endogenous ovarian hormone production alters ETB receptor responses in young women, which is partially mediated by E2. Additional data are needed to determine ETB receptor sensitivity to E2 after menopause.

scholarly journals Minimal role for H1 and H2 histamine receptors in cutaneous thermal hyperemia to local heating in humans

2006 ◽  
Vol 100 (2) ◽  
pp. 535-540 ◽  
Author(s):  
Brett J. Wong ◽  
Sarah J. Williams ◽  
Christopher T. Minson
Keyword(s):  
Blood Flow ◽  
Receptor Antagonist ◽  
Skin Blood Flow ◽  
Local Heating ◽  
Histamine Receptor ◽  
Receptor Activation ◽  
Control Site ◽  
Doppler Flowmetry ◽  
Histamine Receptor Antagonist ◽  
And Control

The precise mechanism(s) underlying the thermal hyperemic response to local heating of human skin are not fully understood. The purpose of this study was to investigate a potential role for H1 and H2 histamine-receptor activation in this response. Two groups of six subjects participated in two separate protocols and were instrumented with three microdialysis fibers on the ventral forearm. In both protocols, sites were randomly assigned to receive one of three treatments. In protocol 1, sites received 1) 500 μM pyrilamine maleate (H1-receptor antagonist), 2) 10 mM l-NAME to inhibit nitric oxide synthase, and 3) 500 μM pyrilamine with 10 mM NG-nitro-l-arginine methyl ester (l-NAME). In protocol 2, sites received 1) 2 mM cimetidine (H2 antagonist), 2) 10 mM l-NAME, and 3) 2 mM cimetidine with 10 mM l-NAME. A fourth site served as a control site (no microdialysis fiber). Skin sites were locally heated from a baseline of 33 to 42°C at a rate of 0.5°C/5 s, and skin blood flow was monitored using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated as LDF/mean arterial pressure. To normalize skin blood flow to maximal vasodilation, microdialysis sites were perfused with 28 mM sodium nitroprusside, and control sites were heated to 43°C. In both H1 and H2 antagonist studies, no differences in initial peak or secondary plateau phase were observed between control and histamine-receptor antagonist only sites or between l-NAME and l-NAME with histamine receptor antagonist. There were no differences in nadir response between l-NAME and l-NAME with histamine-receptor antagonist. However, the nadir response in H1 antagonist sites was significantly reduced compared with control sites, but there was no effect of H2 antagonist on the nadir response. These data suggest only a modest role for H1-receptor activation in the cutaneous response to local heating as evidenced by a diminished nadir response and no role for H2-receptor activation.

Effect of functional electrostimulation on impaired skin vasodilator responses to local heating in spinal cord injury

2009 ◽  
Vol 106 (4) ◽  
pp. 1065-1071 ◽  
Author(s):  
Noortje T. L. Van Duijnhoven ◽  
Thomas W. J. Janssen ◽  
Daniel J. Green ◽  
Christopher T. Minson ◽  
Maria T. E. Hopman ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Skin Blood Flow ◽  
Local Heating ◽  
Axon Reflex ◽  
Doppler Flowmetry ◽  
Cord Injury ◽  
Cutaneous Vascular Conductance ◽  
Functional Electrostimulation

Spinal cord injury (SCI) induces vascular adaptations below the level of the lesion, such as impaired cutaneous vasodilation. However, the mechanisms underlying these differences are unclear. The aim of this study is to examine arm and leg cutaneous vascular conductance (CVC) responses to local heating in 17 able-bodied controls (39 ± 13 yr) and 18 SCI subjects (42 ± 8 yr). SCI subjects were counterbalanced for functional electrostimulation (FES) cycling exercise (SCI-EX, n = 9) or control (SCI-C, n = 9) and reanalyzed after 8 wk. Arm and leg skin blood flow were measured by laser-Doppler flowmetry during local heating (42°C), resulting in an axon-reflex mediated first peak, nadir, and a primarily nitric oxide-dependent plateau phase. Data were expressed as a percentage of maximal CVC (44°C). CVC responses to local heating in the paralyzed leg, but also in the forearm of SCI subjects, were lower than in able-bodied controls ( P < 0.05 and 0.01, respectively). The 8-wk intervention did not change forearm and leg CVC responses to local heating in SCI-C and SCI-EX, but increased femoral artery diameter in SCI-EX ( P < 0.05). Interestingly, findings in skin microvessels contrast with conduit arteries, where physical (in)activity contributes to adaptations in SCI. The lower CVC responses in the paralyzed legs might suggest a role for inactivity in SCI, but the presence of impaired CVC responses in the normally active forearm suggests other mechanisms. This is supported by a lack of adaptation in skin microcirculation after FES cycle training. This might relate to the less frequent and smaller magnitude of skin blood flow responses to heat stimuli, compared with controls, than physical inactivity per se.

Bradykinin does not mediate cutaneous active vasodilation during heat stress in humans

2002 ◽  
Vol 93 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
D. L. Kellogg ◽  
Y. Liu ◽  
K. McAllister ◽  
C. Friel ◽  
P. E. Pérgola
Keyword(s):  
Blood Flow ◽  
Heat Stress ◽  
Receptor Antagonist ◽  
Healthy Subjects ◽  
Ringer Solution ◽  
Vascular Conductance ◽  
Doppler Flowmetry ◽  
Hoe 140 ◽  
Control Body ◽  
Cutaneous Vascular Conductance

To test the hypothesis that bradykinin effects cutaneous active vasodilation during hyperthermia, we examined whether the increase in skin blood flow (SkBF) during heat stress was affected by blockade of bradykinin B2 receptors with the receptor antagonist HOE-140. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for local delivery of drugs in eight healthy subjects. HOE-140 was dissolved in Ringer solution (40 μM) and perfused at one site, whereas the second site was perfused with Ringer alone. SkBF was monitored by laser-Doppler flowmetry (LDF) at both sites. Mean arterial pressure (MAP) was monitored from a finger, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Water-perfused suits were used to control body temperature and evoke hyperthermia. After hyperthermia, both microdialysis sites were perfused with 28 mM nitroprusside to effect maximal vasodilation. During hyperthermia, CVC increased at HOE-140 (69 ± 2% maximal CVC, P < 0.01) and untreated sites (65 ± 2% maximal CVC, P < 0.01). These responses did not differ between sites ( P > 0.05). Because the bradykinin B2-receptor antagonist HOE-140 did not alter SkBF responses to heat stress, we conclude that bradykinin does not mediate cutaneous active vasodilation.

scholarly journals Androgens influence microvascular dilation in PCOS through ET-A and ET-B receptors

2013 ◽  
Vol 305 (7) ◽  
pp. E818-E825 ◽  
Author(s):  
Megan M. Wenner ◽  
Hugh S. Taylor ◽  
Nina S. Stachenfeld
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Vascular Dysfunction ◽  
Local Heating ◽  
Gonadotropin Releasing Hormone ◽  
Ovary Syndrome ◽  
Experimental Conditions ◽  
Doppler Flowmetry ◽  
Receptor Inhibition ◽  
Androgen Suppression

Hyperandrogenism and vascular dysfunction often coexist in women with polycystic ovary syndrome (PCOS). We hypothesized that testosterone compromises cutaneous microvascular dilation in women with PCOS via the endothelin-1 ET-B subtype receptor. To control and isolate testosterone's effects on microvascular dilation, we administered a gonadotropin-releasing hormone antagonist (GnRHant) for 11 days in obese, otherwise healthy women [controls, 22.0 ( 4 ) yr, 36.0 (3.2) kg/m2] or women with PCOS [23 ( 4 ) yr, 35.4 (1.3) kg/m2], adding testosterone (T; 2.5 mg/day) on days 8–11. Using laser Doppler flowmetry and cutaneous microdialysis, we measured changes in skin microcirculatory responsiveness (ΔCVC) to local heating while perfusing ET-A (BQ-123) and ET-B (BQ-788) receptor antagonists under three experimental conditions: baseline (BL; prehormone intervention), GnRHant ( day 4 of administration), and T administration. At BL, ET-A receptor inhibition enhanced heat-induced vasodilation in both groups [ΔCVC control 2.03 (0.65), PCOS 2.10 (0.25), AU/mmHg, P < 0.05]; ET-B receptor inhibition reduced vasodilation in controls only [ΔCVC 0.98 (0.39), 1.41 (0.45) AU/mmHg for controls, PCOS] compared with saline [ΔCVC controls 1.27 (0.48), PCOS 1.31 (0.13) AU/mmHg]. GnRHant enhanced vasodilation in PCOS [saline ΔCVC 1.69 (0.23) AU/mmHg vs. BL, P < 0.05] and abolished the ET-A effect in both groups, a response reasserted with T in controls. ET-B receptor inhibition reduced heat-induced vasodilation in both groups during GnRHant and T [ΔCVC, controls: 0.95 (0.21) vs. 0.51 ( 13 ); PCOS: 1.27 (0.23) vs. 0.84 (0.27); for GnRHant vs. T, P < 0.05]. These data demonstrate that androgen suppression improves microvascular dilation in PCOS via ET-A and ET-B receptors.

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